Figure 4.

Use-dependent block of Na⁺ channels by carisbamate (CRS) and lidocaine (LID). Plots comparing the proposed use-dependent Na⁺ channel-blocking effects of CRS (100–400 µmol·L⁻¹), with those of LID (40–160 µmol·L⁻¹) on peak action potential amplitudes evoked by applying a train of brief depolarizing current injections (1 ms, +2.5 nA) at different stimulus frequencies. Results are plotted as mean action potential amplitude (normalized to control at t= 0) ± SEM versus time; n= 4 for all drug concentrations and frequencies (error bars were within width of points). (A) Concentration- and frequency-dependent effects of CRS at (i) 25 Hz and (ii) 100 Hz stimulus frequencies; inset shows a representative trace of the use-dependent effect of 400 µmol·L⁻¹ CRS at 50 Hz stimulation; (B) shows concentration- and frequency-dependent effects of LID under comparable conditions to (A) at (i) 25 Hz and (ii) 100 Hz stimulation; inset shows use-dependent effect of LID (160 µmol·L⁻¹) at 50 Hz stimulation. Note that for comparable final levels of spike suppression, the onset of block by CRS was notably slower than that produced by LID. Data for 400 µmol·L⁻¹ CRS and 160 µmol·L⁻¹ LID block at 25 and 100 Hz stimulus frequencies were fitted by single exponential functions using a least-squares method. The estimated time constants for block onset (τ) and plateau normalized peak values at the end of the stimulus train (y₀) at the maximum concentrations used (derived from the best fits) are shown.